Disease relevance of Pdlim3

• Adult mice deficient in actinin-associated LIM-domain protein reveal a developmental pathway for right ventricular cardiomyopathy [1].
• The absence of a dystrophic phenotype in these mice suggests that down-regulation of ALP does not participate in facioscapulohumeral muscular dystrophy [2].
• Fine genetic mapping studies demonstrate that ALP occurs on chromosome 4q35, near the heterochromatic locus that is mutated in fascioscapulohumeral muscular dystrophy [3].
• RNA blot hybridization results indicate that the mouse placental ALP is encoded by a gene identical to the gene expressed in mouse liver, kidney, and teratocarcinoma stem cells [4].
• Hepatic toxicity of the extracts was also investigated in the dose of 6 g/kg/day orally for 14 consecutive days by measuring ALP, SGOT and SGPT activity in blood and hepatic histological study [5].

High impact information on Pdlim3

• Here we report that the alpha-actinin-associated LIM protein (ALP; Alp in mice) has an essential role in the embryonic development of the right ventricular (RV) chamber during its exposure to high biomechanical workloads in utero [1].
• Here, we identify actinin-associated LIM protein (ALP), a novel protein in skeletal muscle that contains an NH2-terminal PDZ domain and a COOH-terminal LIM motif [3].
• Interestingly the ALP gene occurs at 4q35 near the heterochromatic region mutated in facioscapulohumeral muscular dystrophy, indicating a possible role for ALP in this disease [2].
• Surprisingly, the ALP knockout mice show no gross histological abnormalities and maintain sarcolemmal integrity as determined by serum pyruvate kinase assays [2].
• Taken together, these results offer an intriguing possibility that ALP up-regulation at the onset of BMP-induced osteogenesis could involve Smad/SIP1 interactions, resulting in the derepression of that gene [6].

Biological context of Pdlim3

• Whereas ALP is expressed as two muscle specific isoforms in mammals and chicken as the result of alternative splicing, a single ALP transcript was found in both muscle and non-muscular tissues of Atlantic salmon [7].
• This resulted in the identification of nine novel genes and ESTs that were induced specifically in osteoblasts, in addition to the well-known markers ALP and osteocalcin [8].
• Cell proliferation and apoptosis, specific activity of ALP, were also measured for growth and differentiation [9].
• Cell number was consistently 20-25% higher than control in MC3T3-E1 cultures expressing the truncated pro alpha 1 (I) gene but ALP activity was only 45% of control [10].
• Deficiency of actinin-associated LIM protein alters regional right ventricular function and hypertrophic remodeling [11].

Anatomical context of Pdlim3

• Actinin-associated LIM protein-deficient mice maintain normal development and structure of skeletal muscle [2].
• On the other hand, Western blot analysis revealed several immunoreactive ALP variants in salmon muscle tissues, including a 45 kDa protein in white and red skeletal muscle and a 37-40 kDa protein in heart and smooth muscle [7].
• At later time-points, large numbers of Cbfa1 + bone marrow cells were still present, but the majority of these were close to new trabecular bone surfaces at sites which showed high levels of ALP activity [12].
• The serum ALP activity begins to increase markedly since the third day in sensitive mice (DBA/2), i.e., when the electron microscopy hepatocytes look very damaged; hepatocytes have lost most of their microvilli; necrotic vesicles, degenerative cytoplasmic organelles, lipid vesicles occurred in numerous hepatocytes [13].
• Firstly, liver ALP activity has been demonstrated in the Disse's spaces, on the membrane of the hepatocytes microvilli whilst serum ALP was still very low [13].

Associations of Pdlim3 with chemical compounds

• It was also observed that the subcutaneous injection dose of 18 microg/kg Tyr-Gly-Gly-Phe-Gly-OH, Tyr-Gly-Gly-Phe-Leu-OH, Tyr-Gly-Gly-Phe-Met-OH, Tyr-Gly-Gly-Phe-Met-NH2 significantly increased the content of femur phosphorous and decreased the activity of ALP of the animals [14].
• Studies of thermostability at 56 and 65 degrees C and sensitivity toward inhibitors (L-phenylalanine, L-homoarginine, L-phenylalanylglycylglycine, and levamisole) do not demonstrate differences in the ALP from lungs or liver of the CBA/J and C57L/J strains [15].
• The cellular proliferation (MTT), the cellular differentiation (alkaline phosphatase activity, ALP), and the intercellular cAMP level were investigated at different time points [16].

Analytical, diagnostic and therapeutic context of Pdlim3

• To study the interactions and function of ALP we used purified recombinant proteins in surface plasmon resonance measurements [17].
• The gene encoding the mouse placental alkaline phosphatase (ALP; orthophosphoric-monoester phosphohydrolase, alkaline optimum, EC 3.1.3.1) is mapped to chromosome 4, based on Southern blot hybridization of the mouse cDNA with DNAs from mouse-Chinese hamster somatic cell hybrids [18].

References